Visual deprivation is one of the most extreme conditions leading brain regions to adopt new functions in response to environmental constraints, that is, to compensate for the loss of a sensory modality. Studies in visually deprived animals and in blind humans have long demonstrated the cross-modal recruitment of the visual cortex to process non-visual information. Yet, little is known about the functional parcellation of the reorganized occipital cortex and its precise role in the processing of non-visual information and in higher cognitive functions. The main aims of the present project are (1) to determine the sensory organization of the occipital cortex in blind subjects, (2) to identify the source of non-visual input to occipital cortex in the blind, and (3) to determine the functional role of the occipital cortex of blind subjects in the processing of non-visual stimuli, particularly when using a sensory substitution device. Using functional Magnetic Resonance Imaging (fMRI), we will examine brain activity related to tactile and auditory stimulation while subjects try to either identify or localize stimuli. This will allow us to determine whether domain specificity exists within the reorganized occipital cortex for sensory modality and/or for identification and localization. Using Diffusion Tensor Imaging (DTI) and Voxel-Based Morphometry (VBM), two relatively novel structural MRI techniques, we will investigate the structural basis of cerebral adaptive changes in blind subjects. VBM will allow us to examine if grey-matter cell density and volume in the blind occipital cortex are the same as those in the occipital cortex of sighted persons;DTI will examine the strength of white-matter fiber tracts projecting to and from occipital cortex in both subject groups, thus determining relative changes in the source of non-visual input in the blind. To test to what extent blindness is accompanied by enhanced non-visual abilities and to determine the functional role of occipital cortex in the blind, we will supplement brain imaging with extended psychophysical evaluations. We will examine the co-variance of behavioral performance with activation of brain regions by tactile or auditory stimulation, and in particular with occipital activation elicited by perception through a visual- to-auditory sensory substitution device. We predict that brain areas that are normally not recruited by sounds can be activated during the use of the sensory substitution device according to the stimuli perceived and/or the task performed and commensurate with proficiency of use. PUBLIC HEALTH RELEVANCE A better understanding of the physiological mechanisms underlying brain and cognitive plasticity in blindness will help to develop more adequate rehabilitation strategies and assistive devices for the blind, such as visual prostheses or sensory substitution devices. In a wider perspective, this will provide us with valuable information regarding brain plasticity in general and how the brain modifies its own organization in response to environmental constraints. This could further inspire the development of neuropsychological and rehabilitation methods for patients with brain injuries.